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BACKGROUND: Amyloidosis, a rare multisystem condition, often requires complex, multidisciplinary care. Its low prevalence underscores the importance of efforts to ensure the availability of high-quality patient education materials for better outcomes. ChatGPT (OpenAI) is a large language model powered by artificial intelligence that offers a potential avenue for disseminating accurate, reliable, and accessible educational resources for both patients and providers. Its user-friendly interface, engaging conversational responses, and the capability for users to ask follow-up questions make it a promising future tool in delivering accurate and tailored information to patients. OBJECTIVE: We performed a multidisciplinary assessment of the accuracy, reproducibility, and readability of ChatGPT in answering questions related to amyloidosis. METHODS: In total, 98 amyloidosis questions related to cardiology, gastroenterology, and neurology were curated from medical societies, institutions, and amyloidosis Facebook support groups and inputted into ChatGPT-3.5 and ChatGPT-4. Cardiology- and gastroenterology-related responses were independently graded by a board-certified cardiologist and gastroenterologist, respectively, who specialize in amyloidosis. These 2 reviewers (RG and DCK) also graded general questions for which disagreements were resolved with discussion. Neurology-related responses were graded by a board-certified neurologist (AAH) who specializes in amyloidosis. Reviewers used the following grading scale: (1) comprehensive, (2) correct but inadequate, (3) some correct and some incorrect, and (4) completely incorrect. Questions were stratified by categories for further analysis. Reproducibility was assessed by inputting each question twice into each model. The readability of ChatGPT-4 responses was also evaluated using the Textstat library in Python (Python Software Foundation) and the Textstat readability package in R software (R Foundation for Statistical Computing

OBJECTIVE: To describe the protocol of a prospective study to test the validity of intermuscular coherence (IMC) as a diagnostic tool and biomarker of upper motor neuron degeneration in amyotrophic lateral sclerosis (ALS). METHODS: This is a multicenter, prospective study. IMC of muscle pairs in the upper and lower limbs is gathered in ∼650 subjects across three groups using surface electrodes and conventional electromyography (EMG) machines. The following subjects will be tested: 1) neurotypical controls; 2) patients with symptomatology suggestive for early ALS but not meeting probable or definite ALS by Awaji Criteria; 3) patients with a known ALS mimic. The recruitment period is between 3/31/2021 and 12/31/2025. Written consent will be sought from the subject or the subjects legally authorized representative during enrollment. RESULTS: The endpoints of this study include: 1) whether adding IMC to the Awaji ALS criteria improve its sensitivity in early ALS and can allow for diagnosis earlier; 2) constructing a database of IMC across different ages, genders, and ethnicities. SIGNIFICANCE: This study may validate a new inexpensive, painless, and widely available tool for the diagnosis of ALS.

OBJECTIVES: The objective of this research was to generate psychometric evidence supporting the myasthenia gravis (MG) symptoms patient-reported outcome (PRO) scales as a fit-for-purpose measure of severity of core symptoms of MG and provide information allowing their meaningful interpretation using data from a phase 3 study in MG. METHODS: Data from the MycarinG study, a phase 3 study of rozanolixizumab in patients with generalized MG who experience moderate to severe symptoms (ClinicalTrials.gov Identifier: NCT03971422) were analyzed with both classical test theory (CTT) and Rasch measurement theory (RMT). Meaningful within-individual change and group-level meaningful change were estimated for three MG Symptoms PRO scales using anchor- and distribution-based methods. Anchor-based methods used patient global impression of severity (PGIS) and change (PGIC) in MG symptoms as anchors. RESULTS: Good measurement properties of the MG Symptoms PRO scales were shown in the sample of 200 participants: good to excellent reliability (test-retest and internal consistency reliability) and validity (associations between items and scores within the MG Symptoms PRO scales and between the MG Symptoms PRO scores and other clinical outcomes-MG ADL, QMG score, MGC score, and MGFA classes-were as expected); and the items showed good coverage of the continuum and fit to the Rasch model. Triangulation of the anchor- and distribution-based method results led to the definition of clinically meaningful within-patient improvement in scores for Muscle Weakness Fatigability (-16.67), Physical Fatigue (-20.00), and Bulbar Muscle Weakness (-20.00), with associated ranges. Benchmarks are also proposed for the interpretation of group-level results. CONCLUSION: The strong psychometric performance of the MG Symptoms PRO scales and the information generated to guide its interpretation supports its use in clinical trials for demonstrating the clinical benefits of new treatments targeting core symptoms

INTRODUCTION: Accurate measurement of myasthenia gravis (MG) severity is required for appropriate clinical monitoring of patients with MG and assessment of the benefit of new treatments in clinical trials. Our objective was to explore how MG severity can be measured and to determine how the newly developed MG Symptoms Patient-Reported Outcome (PRO) instrument complements the available measures of MG severity. METHODS: The conceptual coverage of the Quantitative MG (QMG), MG Composite (MGC), MG-Activities of Daily Living (MG-ADL), and MG Symptoms PRO was scrutinized against core symptoms of MG: muscle weakness in three muscle groups (ocular, bulbar, and respiratory), muscle weakness fatigability, and physical fatigue. Post hoc analyses of the MG0002 study, a Phase 2a clinical trial of rozanolixizumab in adults with moderate to severe generalized MG, included correlation and Rasch model analyses. RESULTS: The qualitative appraisal highlighted that only the MG Symptoms PRO captured physical fatigue. Data from 541 assessments (43 unique patients) were used for the analyses. Correlations ranged between 0.56 and 0.74 for the MG-ADL, QMG, MGC, and MG Symptoms PRO Muscle Weakness Fatigability score, and between 0.20 and 0.71 for the MG Symptoms PRO scores focusing on independent muscle groups. Analyses with the Rasch model estimated a meaningful continuum of severity of MG, including all items, except ocular muscles, from the four instruments. The QMG and MG Symptoms PRO had the broadest coverage of the MG severity continuum. Muscle fatigability and physical fatigue were more characteristic of low severity while bulbar weakness indicated more severe MG. CONCLUSION: The severity of MG can be reflected in a meaningful continuum underpinned by the MG-specific outcome measures. Only ocular muscle manifestations were shown to reflect a possibly different facet of MG severity. With its modular nature and comprehensive content, the MG Symptoms PRO provides complementary informatio

An increasing number of clinical trials are enrolling patients with myasthenia gravis (MG). A lack of standardization in the performance of outcome measures leads to confusion among site research teams and is a source of variability in clinical trial data. MGNet, the NIH-supported Rare Disease Clinical Research Network for MG, views standardization of MG outcome measures as a critical need. To address this issue, a group of experts summarized key outcome measures used in MG clinical trials and a symposium was convened to address issues contributing to outcome measure variability. Consensus recommendations resulted in changes to outcome measure instructions and, in some cases, modifications to specific instruments. Recommended changes were posted for public commentary before finalization. Changes to the MG-Activities of Daily Living, MG-Quality of Life-15r, and MG-Impairment Index were limited to adding details to the administration instructions. Recommendations for proper positioning of participants and how to score items that could not be performed because of non-MG reasons were provided for the MG Composite. The Quantitative MG (QMG) score required the most attention, and changes were made both to the instructions and the performance of certain items resulting in the QMG-Revised. The Postintervention Status was believed to have a limited role in clinical trials, except for the concept of minimal manifestation status. As a next step, training materials and revised source documents, which will be freely available to study teams, will be created and posted on the MGNet website. Further studies are needed to validate changes made to the QMG-Revised.

INTRODUCTION: Social determinants of health (SDOH) are important contributors to health outcomes, and better understanding their impact on individuals diagnosed with rare, chronic diseases with high burden and unmet need is critical. Characterizing SDOH burden can help improve the design of patient support programs (PSPs), using targeted approaches to remove barriers to access. METHODS: This study used a mixed-methods strategy employing a quantitative survey, which was designed based on qualitative interviews, to understand the unmet needs and awareness/utilization of PSPs among individuals living with generalized myasthenia gravis (gMG) and experiencing SDOH barriers. The survey was completed by 38 individuals living with gMG, of which the majority were non-White/Caucasian, unemployed, low income, and enrolled in public insurance. Common SDOH challenges, awareness/utilization of available PSPs, and unmet needs were identified. RESULTS: Financial and mental health concerns were the most common among individuals living with gMG and experiencing SDOH barriers throughout diagnosis, accessing treatment, initiating treatment, and continuing treatment. Awareness and utilization of existing support services were low, especially when accessing treatment. Educational, financial, and personalized support with high human touch were commonly perceived as the most valuable resources. IMPLICATIONS: To better serve the needs of individuals with gMG experiencing SDOH barriers, PSPs should use a targeted approach to offer services tailored to harder-to-reach populations. Further, providers, advocacy groups, manufacturers, and public organizations in the gMG ecosystem should strengthen collaborations with PSPs to enable individuals living with gMG to access the services they need to improve their health outcomes.

Introduction/aimsIt is unknown if patients with neuromuscular diseases prefer in-person or virtual telemedicine visits. We studied patient opinions and preference on virtual versus in-person visits, and the factors influencing such preferences.MethodsTelephone surveys, consisting of 11 questions, of patients from 10 neuromuscular centers were completed.ResultsFive hundred and twenty surveys were completed. Twenty-six percent of respondents preferred virtual visits, while 50% preferred in-person visits. Sixty-four percent reported physical interaction as "very important." For receiving a new diagnosis, 55% preferred in-person vs 35% reporting no preference. Forty percent were concerned about a lack of physical examination vs 20% who were concerned about evaluating vital signs. Eighty four percent reported virtual visits were sufficiently private. Sixty eight percent did not consider expenses a factor in their preference. Although 92% were comfortable with virtual communication technology, 55% preferred video communications, and 19% preferred phone calls. Visit preference was not significantly associated with gender, diagnosis, disease severity, or symptom management. Patients who were concerned about a lack of physical exam or assessment of vitals had significantly higher odds of selecting in-person visits than no preference.DiscussionAlthough neither technology, privacy, nor finance burdened patients in our study, more patients preferred in-person visits than virtual visits and 40% were concerned about a lack of physical examination. Interactions that occur with in-person encounters had high importance for patients, reflecting differences in the perception of the patient-physician relationship between virtual and in-person visits.

DMD pathogenic variants for Duchenne and Becker muscular dystrophy are detectable with high sensitivity by standard clinical exome analyses of genomic DNA. However, up to 7% of DMD mutations are deep intronic and analysis of muscle-derived RNA is an important diagnostic step for patients who have negative genomic testing but abnormal dystrophin expression in muscle. In this study, muscle biopsies were evaluated from 19 patients with clinical features of a dystrophinopathy, but negative clinical DMD mutation analysis. Reverse transcription-polymerase chain reaction or high-throughput RNA sequencing methods identified 19 mutations with one of three pathogenic pseudoexon types: deep intronic point mutations, deletions or insertions, and translocations. In association with point mutations creating intronic splice acceptor sites, we observed the first examples of DMD pseudo 3'-terminal exon mutations causing high efficiency transcription termination within introns. This connection between splicing and premature transcription termination is reminiscent of U1 snRNP-mediating telescripting in sustaining RNA polymerase II elongation across large genes, such as DMD. We propose a novel classification of three distinct types of mutations identifiable by muscle RNA analysis, each of which differ in potential treatment approaches. Recognition and appropriate characterization may lead to therapies directed toward full-length dystrophin expression for some patients.

ObjectiveTo determine whether locally acting ACE-083 is safe, well tolerated, and increases muscle volume, motor function, and quality of life (QoL) in adults with Charcot-Marie-Tooth disease (CMT) type 1.MethodsThis phase 2 study enrolled adults with CMT1 or CMTX (N=63). Part 1 was open-label and evaluated safety and tolerability of different dose levels of ACE-083 for use in Part 2. Part 2 was a randomized, placebo-controlled, 6-month study of 240 mg/muscle ACE-083 injected bilaterally in the tibialis anterior muscle, followed by a 6-month, open-label extension in which all patients received ACE-083. Pharmacodynamic endpoints included total muscle volume (TMV; primary endpoint), contractile muscle volume (CMV), and fat fraction. Additional secondary endpoints included 6-minute walk test, 10-meter walk/run, muscle strength, and QoL. Safety was assessed with treatment-emergent adverse events (TEAEs) and clinical laboratory tests.ResultsIn Part 1 (n=18), ACE-083 was generally safe and well tolerated at all dose levels, with no serious AEs, TEAEs ≥Grade 3, or death reported. In Part 2 (n=45 enrolled, n=44 treated), there was significantly greater change in TMV with ACE-083 compared with placebo (LS mean difference: 13.5%; p = 0.0096). There was significant difference between ACE-083 and placebo for CMV and change in ankle dorsiflexion strength. Fat fraction and all other functional outcomes were not significantly improved by ACE-083. Moderate-to-mild injection-site reactions were the most common TEAEs.ConclusionsDespite significantly increased TMV and CMV, patients with CMT receiving ACE-083 in tibialis anterior muscles did not demonstrate greater functional improvement compared with those receiving placebo.Classification of evidenceThis study provides Class II evidence that intramuscular ACE-083 is safe, well tolerated, and increases total muscle volume after 6 months of treatment in adults with CMT1 or CMTX.

Musik-applikationen c3n play används på surfplattor och mobiltelefoner som har den kapacitiva pekskärmstypen. I dagsläget kan musik-applikationen enbart styras med fingrarna. Spelpjäser, utvecklades för att målgruppen skulle kunna kombinera fingerinmatning med något fysiskt och för att underlätta spelandet. En konvergerande produktutvecklingsprocess innefattande faser och aktiviteter tillämpades. Inledningsvis genomfördes en detaljerad informationsinsamling som grund för det fortsatta arbetet. Analys av konkurrenternas produkter och en benchmarking implementerades, för att både identifiera kraven som ställts på produkten och upprätta en kravspecifikation. Spelpjäsen delades in i tre delar: formen på hela spelpjäsen, mönster som gör att användarna kan identifiera varje spelpjäs och mönster på undersidan som programvaran kunde identifiera. Därefter genererades flera idéer på formen av spelpjäsen, vilka utvärderades med hänsyn till de uppsatta kraven. Idéer som ansågs uppfylla kraven bäst gick vidare till konceptgenereringsfasen, där fem olika förslag kunde visualiseras i skisser och CAD-modeller (Computer Aidid Design). Koncepten utvärderades och förbättrades för att tillfredsställa användarnas behov och förväntningar. Det slutliga konceptet på formen gjordes i fyra olika varianter, vilka framställdes som prototyper för vidare test av målgruppen. Konceptlösningar på spelpjäsens identifieringsmönster av användaren analyserades för att passa in i c3n play-användargränssnitten. Tekniken för att identifiera spelpjäsen mot den kapacitiva pekskärmstypen utvecklades via tester, där avstånd och vinklar på kontaktpunkterna bestämdes. Viktiga produktutvecklingsverktyg implementerades för att säkerställa såväl spelpjäsernas hållbarhet som miljövänlighet, med hänsyn till produktlivscykel, tillverkning, montering och tillförlitlighet samt kostnadsmedvetenhet. Därefter valdes lämpliga material samt en lämplig tillverkningsmetod. Detta resulterade i en produktfamilj bestående av ått, The application c3n play can be used on tablets and mobile phones that have capacitive multi touchscreens. The application can only be controlled by using the finger input. Tangible user interface was developed so the target group can use something physically “checkers” in a combination with the finger input. A product development process comprising phases and activities was implemented. Initially a detailed information collection were conducted and used as underlying to the continued work. Competitors’ products were analyzed and a benchmarking was implemented to identify user needs and to be able to make a target specification. Checkers was divided in three parts, shape of the whole checker, pattern so users can identify every checker and a pattern on the bottom so the software can identify the checkers on the screen. After that ideas were generated and the shape of the checker was evaluated. Ideas that was considered to meet the user needs went on to concept generation phase, where five different proposals was visualized in sketches and CAD (Computer Aided Design) - models. Concepts was evaluated and improved to satisfy customer needs and expectations. Final concept of the shape was developed into four different variants that was prepared as prototypes for further testing by target group. Concept solutions on identification pattern was analyzed to fit c3n play user interface. Technology to identify the checker against capacitive screen was developed by tests. Where distance and angles of contact points was determined. Important product development tools was implemented to ensure the checkers sustainability. With respect to the product life cycle, environment, manufacturing, assembly, reliability and cost consciousness. Suitable materials and manufacturing method was then chosen. Resulted in a product family consisted of eight different checkers. Each checker can change a different function in the c3n play-application. Amplitude, Resonance, Highpassfilter, Low-pass

The objective of the study was to evaluate the effect of veneering zirconia surfaces with feldspar-based ceramics or glass ceramics on bond strength when using a resin composite cement. Forty-eight ytteria tetragonal zirconia polycrystal (Y-TZP) specimens were randomly divided into four groups. Six pairs were created in each group by bonding two of the specimens to each other after having the bonded surfaces treated differently as the following: I) polished and heat-treated (served as control), II) veneered with Vita VM9, III) veneered with e.max CAD Glaze and, IV) polished and heat-treated. The luting agent used in Group I - III was RelyX Unicem and in Group IV Charisma. Using a universal testing machine, the load at debonding (Newton) was recorded and the bond strength (MPa) was then calculated. Group I exhibited statistical significantly superior bond strength compared to all other groups. A statistical significantly superior bond strength was seen for the specimens in Group II compared to Group III and IV. Group IV presented the lowest bond strength but there was no significant difference to Group III. The present paper show no promotion in bond strength when zirconia was veneered with feldspar-based ceramic or glass ceramic.

By the late of 2007, the port of Gavle authorities found out that the harbor capacity was not enough, and needs to be increased. This could be done by having new ports area, building new facilities and dredging the bottom of the sea near the harbor. The dredging of sediment will improve the navigation at the port. The upper layer of dredged sediment was found to be contaminated with harmful materials such as TBT, PCBs and metal parts. These sediments had to be amended with cement, fly ash and merit5000. The stabilized material were used as a backfill in reclamation of new areas for terminal expansion.The aim of this study was to evaluate the interaction between the stabilized materials and the steel sheet pile wall. The cone penetration test data were used to evaluate the geotechnical parameters of the backfill material. Analytical calculations were used to illustrate the design of the sheet pile wall. Finite element method (PLAXIS 2D) was used to analyze the interaction of the sheet pile wall with the stabilized material., Validerat; 20121030 (anonymous)